A Double-Blind Study of Amantadine Hydrochloride versus Benztropine Mesylate in Drug-Induced Parkinsonism

Kelly, John; Zimmermann, Robert; Abuzzahab, F. S.; Schiele, Burtrum C.

doi:10.1159/000136523

Cited by 19 publications

(5 citation statements)

References 6 publications

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“…Benztropine, which is in common use, and ethopropazine, which may not be widely available, are anticholinergic medications known to be effective for parkinsonism. Amantadine at 100‐400 mg daily also has good support in the literature, and may be particularly helpful in elderly patients who need to avoid anticholinergic effects.…”

Section: Specific Adverse Effectsmentioning

confidence: 93%

Management of common adverse effects of antipsychotic medications

2018

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The benefits of antipsychotic medications are sometimes obscured by their adverse effects. These effects range from relatively minor tolerability issues (e.g., mild sedation or dry mouth) to very unpleasant (e.g., constipation, akathisia, sexual dysfunction) to painful (e.g., acute dystonias) to disfiguring (e.g., weight gain, tardive dyskinesia) to life-threatening (e.g., myocarditis, agranulocytosis). Importantly, adverse effect profiles are specific to each antipsychotic medication and do not neatly fit into first- and second-generation classifications. This paper reviews management strategies for the most frequent side effects and identifies common principles intended to optimize net antipsychotic benefits. Only use antipsychotics if the indication is clear; only continue antipsychotics if a benefit is discernible. If an antipsychotic is providing substantial benefit, and the adverse effect is not life-threatening, then the first management choice is to lower the dose or adjust the dosing schedule. The next option is to change the antipsychotic; this is often reasonable unless the risk of relapse is high. In some instances, behavioral interventions can be tried. Finally, concomitant medications, though generally not desirable, are necessary in many instances and can provide considerable relief. Among concomitant medication strategies, anticholinergic medications for dystonias and parkinsonism are often effective; beta-blockers and anticholinergic medications are useful for akathisia; and metformin may lead to slight to moderate weight loss. Anticholinergic drops applied sublingually reduce sialorrhea. Usual medications are effective for constipation or dyslipidemias. The clinical utility of recently approved treatments for tardive dyskinesia, valbenazine and deutetrabenazine, is unclear.

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Section: Specific Adverse Effectsmentioning

confidence: 93%

Management of common adverse effects of antipsychotic medications

2018

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“…Mindham et al (1972) found that amantadine and orphenadrine were no more effective than placebo in alleviating phenothiazine-induced extrapyramidal symptoms. DiMascio et al (1976), Kelly et al (1974) and Merrick and Schmitt (1973), comparing amantadine with benztropine mesylate, could show no difference in therapeutic effects, but these studies had no placebo control. However, Pacifici et al (1976), using a double-blind crossover design, observed that amantadine was more effective than placebo in alleviating rigidity, tremor, hypokinesia and vegetative disturbances.…”

Section: Drug-induced Extrapyramidal Symptomsmentioning

confidence: 99%

“…By accident, Schwab et al (1969) discovered that amantadine also ameliorated the symptoms of Parkinson's disease, for which purpose its efficacy has also been demonstrated in controlled trials and for which it is now recommended (Parkes 1974). Finally, data suggest that oral amantadine ameliorates extrapyramidal symptoms induced by neuroleptic drugs (DiMascio et al 1976;Kelly et al 1974;Merrick & Schmitt 1973), although this has been challenged (Mindham et al 1972). These diverse pharmacological effects of amantadine are probably mediated by the unaltered compound, since amantadine metabolites have only been detected in human urine in small quantities (Koppel & Tenczer 1985).…”

mentioning

confidence: 99%

Clinical Pharmacokinetics of Amantadine Hydrochloride

Aoki

Sitar

1988

Clinical Pharmacokinetics

188

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Amantadine is a drug with diverse uses ranging from prevention of influenza A illness to the treatment of patients with Parkinson's disease. It is available only in oral formulations from which it is well absorbed and widely distributed, little drug being present in the circulation. Apparent volume of distribution is inversely related to dose over the therapeutic range and accounts in part for a noteworthy logarithmic increase in plasma concentration as a function of dose. Elimination is primarily by renal clearance by both glomerular filtration and tubular secretion. Amantadine accumulates in patients with renal dysfunction. Hence, doses must be reduced in such patients to avoid toxicity. Interactions with other drugs appear uncommon. Relationships have been demonstrated between amantadine therapeutic effects and plasma concentrations in different study cohorts, but not in individual patients. Dose schedules have been suggested for individuals in whom amantadine kinetics are different from healthy subjects. However, these schedules are controversial in their choice of target concentrations and in being untested as to predictive value.

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“… 51 One double-blind crossover study found no difference in efficacy between amantadine and benztropine. 83 In another double-blind study, amantadine was found to have fewer side effects than and comparable efficacy to benztropine in treating DIP, with the exception of benztropine having a greater effect on rigidity. 84 Additionally, a systematic review provided Level C evidence for the use of amantadine in tardive syndromes.…”

Section: Treatmentmentioning

confidence: 98%

Updated Perspectives on the Management of Drug-Induced Parkinsonism (DIP): Insights from the Clinic

Feldman¹,

Marmol²,

Margolesky³

2022

TCRM

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Parkinsonism refers to the clinical combination of bradykinesia, rigidity, tremor, and postural instability. Parkinsonism is often neurodegenerative, but it can be secondary or iatrogenic, as in drug-induced parkinsonism (DIP), which is the topic of this review. We review the pathophysiology of DIP, differentiate DIP and idiopathic Parkinson’s disease (PD), list culprit medications in the development of DIP, discuss the diagnosis of DIP as well as the motor and nonmotor signs and symptoms that can help with differentiation of DIP and PD, and detail the management of DIP.

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A Double-Blind Study of Amantadine Hydrochloride versus Benztropine Mesylate in Drug-Induced Parkinsonism

Cited by 19 publications

References 6 publications

Management of common adverse effects of antipsychotic medications

Management of common adverse effects of antipsychotic medications

Clinical Pharmacokinetics of Amantadine Hydrochloride

Updated Perspectives on the Management of Drug-Induced Parkinsonism (DIP): Insights from the Clinic

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